Structure of 3333-15-1
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CAS No. : | 3333-15-1 |
Formula : | C15H14O2 |
M.W : | 226.27 |
SMILES Code : | O=C(O)C(C1=CC=CC=C1)CC2=CC=CC=C2 |
MDL No. : | MFCD00044405 |
Boiling Point : | No data available |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83 % ee | With 5%-palladium/activated carbon; hydrogen; benzylamine; Cinchonidin In 1,4-dioxane; water at 22.84℃; | General procedure: A 5percentPd/C catalyst was obtained from N.E. Chemcat (5percent STD type)in a 51percent wet form, and stored at 280 K until use. PCA (1) wasused after recrystallization from acetone, and all the other substrates(2–9) were prepared by Perkin reaction using a methodreported [15]. The hydrogenation conditions were as follows.5percentPd/C (23 mg calculated as a dry form, 10 mol of Pd) was pretreatedat 353 K in wet dioxane (dioxane containing v/v 2.5percent water)under atmospheric hydrogen for 30 min. After cooling to 296 K,CD (0.05–100 mol) in wet dioxane was added to the catalyst.A substrate (0.5 mmol) and then benzylamine (1.0 equiv.) in wetdioxane were added (total amount of the solvent = 10 ml) to the CDmodifiedcatalyst with stirring. Within 3–6 h the substrate was fullyconverted to the expected products at 296 K under 105 Pa of hydrogen.The product eepercent were determined by chiral high performanceliquid chromatography (HPLC). The relative initial hydrogenationrates were determined at 25percent conversion by measuring hydrogenconsumption and normalized to the corresponding rates at 0-M ofCD (relative initial rate = observed initial rate over the modified catalyst/the initial rate over the unmodified catalyst). HPLC conditionsare shown in Table 1. |
82 % ee | Stage #1: With 5%-palladium/activated carbon; hydrogen; benzylamine; Cinchonidin In 1,4-dioxane; water at 22.84 - 79.84℃; for 2 h; Stage #2: With hydrogenchloride In water |
General procedure: All chemicals were purchasedfrom commercial sources andpurified viadistillation when necessary. 6-hydroxy CD (6-OHCDin Scheme 1) was preparedfrom QN via de-methylation(55percentyield). The enantioselective hydrogenation reactions ofPCA and DMPCA were carried out over chiral modified Pd/Casfollows.4,9Astirring suspension of 5percentPd/C (43 mg as a50percentcontent, wetform, STD-type supplied by N.E. Chemcat)and 5 mL of 2.5percentH2O-containing dioxane was heated under105Pa ofhydrogen at 353 Kfor 30 min. After cooling to 296 K,asolution of modifier (0.001512 mg)in the solvent (1 mL)was added. After 30 min, 0.5 mmol of the substrate acidinthe solvent (4 mL) and then benzylamine (BnNH2,55L) wasadded. The Pd/substrate molar ratio was 10/500 (inmolin10mL of polar wet dioxane). The reaction temperature and pressure were 296 K and 105Pa of hydrogen, respectively. Thecatalytic activity was calculated from the rate of hydrogenconsumption at 25percentconversion. The hydrogen consumptioncontinuedfor 13h. After additional 2h, a 2M HCl aqueoussolution (1 mL) was added to the solution,followed byfiltration ofthe reaction mixture to remove the catalyst. Thefiltratewas extracted with ethyl acetate (2 mL) and washed with water(2 mL). The extract was analyzed by HPLC with a chiral column (Daicel OJ-3for PCA and AD-3for DMPCA). |
54 % ee | Stage #1: With 5%-palladium/activated carbon; hydrogen; benzylamine; (+)-cinchonine In 1,4-dioxane; water at 22.84℃; |
General procedure: All chemicals were purchasedfrom commercial sources andpurified viadistillation when necessary. 6-hydroxy CD (6-OHCDin Scheme 1) was preparedfrom QN via de-methylation(55percentyield). The enantioselective hydrogenation reactions ofPCA and DMPCA were carried out over chiral modified Pd/Casfollows.4,9Astirring suspension of 5percentPd/C (43 mg as a50percentcontent, wetform, STD-type supplied by N.E. Chemcat)and 5 mL of 2.5percentH2O-containing dioxane was heated under105Pa ofhydrogen at 353 Kfor 30 min. After cooling to 296 K,asolution of modifier (0.001512 mg)in the solvent (1 mL)was added. After 30 min, 0.5 mmol of the substrate acidinthe solvent (4 mL) and then benzylamine (BnNH2,55L) wasadded. The Pd/substrate molar ratio was 10/500 (inmolin10mL of polar wet dioxane). The reaction temperature and pressure were 296 K and 105Pa of hydrogen, respectively. Thecatalytic activity was calculated from the rate of hydrogenconsumption at 25percentconversion. The hydrogen consumptioncontinuedfor 13h. After additional 2h, a 2M HCl aqueoussolution (1 mL) was added to the solution,followed byfiltration ofthe reaction mixture to remove the catalyst. Thefiltratewas extracted with ethyl acetate (2 mL) and washed with water(2 mL). The extract was analyzed by HPLC with a chiral column (Daicel OJ-3for PCA and AD-3for DMPCA). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75 % ee | With cinchonidine; 5% Pd/CNT; hydrogen; benzylamine In 1,4-dioxane; water | General procedure: Hydrogenation was carried out in a magnetically stirred autoclave in 1,4-dioxane containing 2.5percent (v/v) of water under an atmospheric pressure of hydrogen at room temperature. The catalyst (20mg) was pre-treated in a H2 flow at 375°C for 30min. After cooling down and transferred to the autoclave, the catalyst was pre-treated with modifier CD (0.02mmol) in 4mL solvent for an additional 30min. Then, certain amount of substrate and BA, as an effective additive, in 2mL solvent were added to the mixture. After adjusting the hydrogen pressure to the desired H2 pressure, the stirring was started. For substrates 1–4, the mixture after reaction was first neutralized with a diluted HCl solution, extracted with ethyl ether and analyzed by hydrogen nuclear magnetic resonance (1H NMR, Bruker DRX 400MHz type spectrometer) for conversion and a high performance liquid chromatography (HPLC, 6890 Agilent Co.) equipped with a chiral column (Daicel Chiralcel OJ-H) for enantiomeric excess (ee). For substrates 5 and 6, the mixture after reaction was first neutralized with a diluted HCl solution. Then, the catalyst and liquid were separated by centrifugation. After passing the liquid phase through a short silica column and drying, the conversion and enantioselectivity of 5 or 6 were determined on a gas chromatograph (Agilent 6890, 30m×0.32mm×0.25μm HP19091G-B213 capillary column). |
80 % ee | With hydrogen; benzylamine In 1,4-dioxane; water at 22.84℃; | General procedure: The substrate α-phenylcinnamic acid (PCA, Aldrich; 98 percent) was purified by crystallization from acetone solution. p,p'-Dimethoxyphenylcinnamic acid (DMPCA) was synthesized from p-anisaldehyde and p-methoxyphenylacetic acid by the Perkin reaction and characterized by nuclear magnetic resonance (NMR), as reported previously [34]. Solvents (Wako Pure Chemicals; special grade), cinchonidine (CD, Wako Pure Chemicals; 99 percent), and benzylamine (BA, WakoPure Chemicals, 98 percent) were used as received. Enantioselective hydrogenation of PCA or DMPCA was conducted as reported in our previous study [28]. Typically, wet 5 percent Pd/C (23 mg as dry form, 0.01 mmol of Pd) was pretreated in 5 ml wet dioxane (dioxane containing 2.5 percent water) at 353 K under atmospheric pressure of H2 for 30 min. After the catalyst had cooled to 296 K, CD (0 or 0.02 mmol) in wet dioxane was added to the catalyst. The resulting suspension was then stirred for 30 min, while the H2 atmosphere was maintained. Next, the substrate (PCA or DMPCA, 0.5 mmol) and then BA (0.3 mmol) was injected into the reactor. Hydrogen uptake was measured, while the reaction solution was maintained under atmospheric pressure of H2 in order to monitor the progress of the reaction. Hydrogenation rates were determined at 20–25 percent conversion of the substrate. In another hydrogenation procedure, the catalyst and CD were prereduced at 296 K by stirring for 30 min in 5 ml of the solvent under H2 atmosphere prior to substrate injection, followed by BA addition. This latter procedure is called ‘‘without the pretreatment’’ here. The product eepercent was determined via high-performance liquid chromatography (HPLC) [Daicel Chiralpak OJ-H; 25 cm 9 4.6 mm; Hex/IPA/TFA = 95/5/0.1, retention times: 15.4 min (R) and 24.4 min (S) at a flow rate of 1 mL/min], and the final reaction conversions were determined via 1H NMR (600 MHz) spectroscopy. After washing each portion with 1 N HCl, the reaction mixture was found to contain only the substrate and the corresponding hydrogenation products. The enantiomeric excess (eepercent) was calculated according to the following equation: eepercent 100 x SR=[S] - [R]; where [S] and [R] represent the concentrations of S- and R-enantiomers, respectively. |
58 % ee | With 5%-palladium/activated carbon; hydrogen; benzylamine; Cinchonidin In 1,4-dioxane; water at 22.84℃; | The enantioselective hydrogenation of PCA was conductedat 296 K as reported in our previous study after one of the following pretreatments employed previously; Pretreatment(A): wet 5 percent Pd/C (23 mg as a dry form, 0.01 mmol of Pd) was pretreated at 353 K in 5 mL of wet dioxane (dioxanecontaining 2.5 percent water) under an atmospheric pressure of H2 for 30 min. After the catalyst was cooled to 296 K, CD(0.02 mmol) in wet dioxane (1 mL) was added to the catalyst. The resulting suspension was then stirred for 30 min, whilethe H2-atmosphere was maintained. Next, the substrate (PCA,0.5 mmol) and then BA (0.3 mmol) were successively injectedinto the reactor through a septum port. Pretreatment (B): Pd/Cin the reactor was evacuated at room temperature (rt) with a diaphragm pump at 13 kPa for 10 min, which was sufficient time to reach a stationary state. After quickly flashing with H2,dioxane (1 mL) was added to Pd/C, followed by evacuation for 10 min and subsequent quick flashing with H2 (the coevaporation treatment). Wet dioxane (5 mL) was added prior to the CD modification. A solution of CD (0.02 mmol) in wet dioxane (1 mL) was added to the pretreated catalyst, and stirred for 30 min under an atmospheric pressure of H2. PCA (0.5 mmol) in wet dioxane (4 mL) and then BA (0.5 mmol) were added to the reactor via the septum port. Pretreatment(C): as employed in our earlier study, the catalyst and CD were pretreated at 296 K in 5 mL of the solvent, while stirring for 30 min under H2-atmosphere prior to the injection of PCA (0.5 mmol) in wet dioxane (4 mL), followed by 0.5 mmol of BA addition. After one of the above pretreatments, the rate of H2-uptake was measured to monitor the progress of the reaction, while the reaction solution was maintained under anatmospheric pressure of H2. Hydrogenation rates were determined at a 20–25 percent conversion of the substrate. The product enantioselectivity expressed by percent eewas determined via HPLC (Daicel Chiralpak OJ-H;25 cm × 4.6 mm; Hex/IPA/TFA = 95/5/0.1, retention times:15.4 min (R) and 24.4 min (S) at a flow rate of 1 mL/min),and the final reaction conversions were determined via 1H-NMR (600 MHz) spectroscopy. After washing each portion with an aqueous solution of 1 N HCl, the reaction mixture was found to contain only the substrate and the hydrogenation products. The enantiomeric excess (percent ee) was calculated according to the following equation. percent ee = 100×([S]-[R]) / ([S]+[R]) , where [S] and [R] represent the concentrations of S- and R-enantiomers, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
500 mg | With lithium hydroxide monohydrate; dihydrogen peroxide In tetrahydrofuran; water at 20℃; for 4.5 h; | Step 3: (2S)-2,3-Diphenylpropanoic acid: To a well stirred solution of step 2 intermediate (1.3 g, 3.376 mmol) in a mixture of THF (80 ml) and water (20 ml) was added hydrogen peroxide (10 ml) and lithium hydroxide monohydrate (142 mg, 3.376 mmol) at 0 °C and was stirred for 4.5 h at room temperature. The reaction mixture was acidified with dilute HC1, diluted with water (150 ml) and extracted with ethyl acetate (2 x 250 ml). The combined organic layer was washed with water (3 x 100 ml), brine (100 ml), dried (Na2S04), filtered and concentrated to yield the product which was further purified by column chromatography to yield 500 mg of the product as off-white solid; 1H NMR (300 MHz, OMSO-d6) δ 2.90-2.97 (m, 1H), 3.23-3.29 (m, 1H), 3.86 (t, / = 7.2 Hz, 1H), 7.14-7.22 (m, 6H), 7.25-7.32 (m, 4H), 12.34 (br s, 1H). HPLC: Chiracel OD-H, retention time: 15.09 min (hexane/EtOH, 98:2, 99.52 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87 % ee | With benzoic acid anhydride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 6 h; Resolution of racemate | Experimental Example 4Production of Optically Active Ester and Optically Active Carboxylic Acid Using 1,1-di(9-phenanthryl)methanol As shown in the above reaction equation, an optically active ester and optically active carboxylic acid are obtained by reacting 1,1-di(9-phenanthryl)methanol and various racemic carboxylic acids. The results are shown in Table 4.; Entry 38di(9-phenanthryl)methyl (R)-2,3-diphenylpropanoateHPLC of 2,3-diphenylpropan-1-ol derived from the title compound (CHIRALPAK AD-H, i-PrOH/hexane=1/9, flow rate=0.5 mL/ml): tR=14.7 min (93.4percent), tR=18.7 min (6.6percent);IR (KBr): 3064, 1723, 1495, 1451, 1145, 748, 726 cm-1;1H NMR (CDCl3): δ8.79-8.55 (m, 4H, Ph), 8.29 (s, 1H, 1'-H), 7.90-7.80 (m, 1H, Ph), 7.71-7.10 (m, 23H, Ph), 4.10 (dd, J=10.0, 5.4 Hz, 1H, 2-H), 3.54 (dd, J=13.9, 10.0 Hz, 1H, 3-H), 3.02 (dd, J=13.9, 5.4 Hz, 1H, 3-H);13C NMR (CDCl3): δ172.3, 139.1, 138.4, 132.6, 132.5, 131.0, 131.0, 130.8, 130.6, 130.6, 130.4, 130.1, 129.7, 129.2, 129.1, 129.0, 128.9, 128.4, 128.3, 128.3, 127.9, 127.6, 127.3, 127.2, 127.0, 126.9, 126.9, 126.6, 126.5, 126.4, 126.4, 126.1, 124.3, 123.9, 123.3, 123.1, 122.4, 122.3, 71.3, 53.7, 39.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73 % ee | With benzoic acid anhydride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 6 h; Resolution of racemate | Experimental Example 3Production of Optically Active Ester and Optically Active Carboxylic Acid Using 1,1-di(1-naphthyl)methanol As shown in the above reaction equation, an optically active ester and optically active carboxylic acid were obtained by reacting 1,1-di(1-naphthyl)methanol and various racemic carboxylic acids. The results are shown in Table 3.; Entry 26di(1-naphthyl)methyl (R)-2,3-diphenylpropanoateHPLC (CHIRALPAK AD-H, i-PrOH/hexane=1/9, flow rate=0.75 mL/min); tR=12.3 min (13.5percent), tR=23.1 min (86.5percent);IR (neat): 3033, 1736, 1600, 1511, 780, 678 cm-1;1H NMR (CDCl3): δ8.15 (s, 1H, 1'-H), 7.78-7.56 (m, 5H, Ph), 7.49 (t, J=8.3 Hz, 1H, Ph), 7.38-7.14 (m, 11H, Ph), 7.13-6.94 (m, 5H, Ph), 6.76 (dd, J=7.5 Hz, 1H, Ph), 7.06 (d, J=10.5, 7.0 Hz, 1H, Ph), 3.94 (dd, J=10.0, 5.5 Hz, 1H, 2-H), 3.40 (dd, J=13.7, 10.0 Hz, 1H, 3-H), 2.92 (dd, J=13.7, 5.5 Hz, 1H, 3-H);13C NMR (CDCl3): δ172.4, 139.0, 138.2, 134.35, 134.30, 133.7, 133.6, 131.0, 130.8, 129.0, 128.9, 128.68, 128.63, 128.57, 128.4, 128.3, 128.1, 127.5, 126.7, 126.33, 126.31, 126.0, 125.7, 125.6, 125.20, 124.97, 123.4, 123.3, 71.4, 53.6, 39.2;HR MS: calculated for C36H28O2Na (M+Na+)=515.1982, found 515.1963.(S)-2,3-diphenylpropionic acidHPLC (CHIRALPAK AD-H, i-PrOH/hexane/TFA=1/10/0.01, flow rate=0.75 mL/min); tR=12.5 min (21.9percent), tR=15.5 min (78.1percent);1H NMR (CDCl3): δ10.35 (br s, 1H, COOH), 7.28-6.98 (m, 10H, Ph), 3.78 (dd, J=8.2, 7.0 Hz, 1H, 2-H), 3.33 (dd, J=13.8, 8.2 Hz, 1H, 3-H), 2.96 (dd, J=13.8, 7.0 Hz, 1H, 3-H). |